Biology Questions, Quiz Example

There are consequences of receiving an observation in a regulatory audit/inspection. Describe the consequences that may occur if an observation is received. Also, describe the 3 categories of observations and list at least two examples of each. Ten answers are expected for this question.

The Food and Drug Administration will issue a FDA Form 483 to firm management at the end of an inspection when the audit has found an observation of any type of condition in their judgment that falls within the Food Drug and Cosmetic Act and other related Acts. Any observation made indicates that a food, drug, cosmetic or device has not been prepared, packed or help at the standard conditions and is indicated as injurious to health. When this occurs, the FDA form is given to the company’s management and the form is discussed with the company. The company must respond to the FDA in writing with a corrective action plan that will fix the observations noted. The final determination is not the final decision. The FDA uses the report and any other evidence collected in the inspection, as well as the company’s response in determining if any further action is needed in order to protect the health of the consumers.

There are three different types of FDA observations: NAI (No Action Indicated), VAI (Voluntary Action Indicated) and OAI (Official Action Indicated). Below I will list each observation with two examples.

NAI or No Action Indicated is observation that indicates that there were no objectionable conditions found during the inspection. These are still observations; however, they are observations of deviations that are in the Investigators judgment that are questionable. An example would be a change in a procedure for filing Standard Operating Procedures (SOPs). In addition, another example would include a change in the room temperature from that indicated on the SOP.

VAI or Voluntary Action Indicated occurs when there are objectionable conditions; however, the FDA is not prepared to take or recommend any regulatory action at that time. An example of a VAI observation would include failure to follow Standard Operating Procedures for freezer reading for one of the five freezers for a significant amount of time as a specific product was on hold. Another example would include Corrective Actions not signed in the regulated amount of time period by authorized personnel.

OAI or Official Action Indicated is an observation that occurs when the regulatory agency will recommend sanctions. An example of an OAI could occur when a medical device resulted in total failure of system areas in management controls. Another example would include failure of the company to submit a death or serious injury MDR report to the FDA.

Subject Recruitment Exercise – This question contains 5 parts.

Situation: Investigators frequently misjudge the extent of their potential subject pool because they have failed to take into account the effects of all enrollment criteria or they have incompletely understood the implications of those criteria.

Directions: Indicate which of the following studies are likely to have enrollment difficulties and provide an explanation for each of your answers using complete sentences.

1. a) A Phase 3 study of a new prostaglandin inhibitor for menstrual cramps. Excluded from the study are males, pre- and post-menarcheal females, and menarcheal females with gastric ulcers or a known sensitivity to compounds similar to the investigational drug.

The above study might have enrollment issues due to the lack of awareness of the study. In addition, menstrual cramps are not a medical condition that most women go to the doctor for since there are over the counter medications. Furthermore, the study excludes a large sample size, such as males, and pre and post menarcheal females, as well as any women with certain conditions.

1. b) A Phase 2 study of an analgesic conducted at an inner city clinic. Males and females 18 years and older are eligible to participate as long as they have no known sensitivity to the drug class being tested. Patients must keep a diary in which they describe the effect of the medication (e.g., “Relieved pain for two hours”). The information in the diary will constitute the efficacy measure of the drug.

 The study is geared toward enrollment of both male and females from an inner city clinic starting at the age of 18. Therefore, the study may have trouble with enrollment due to the area of the clinic. It has been found that enrollment is lower with underprivileged and lower income participants and given that the clinic is inner city, it is most likely that the participants would be of lower income and lower educational standing. In addition, there may be a language barrier that may deter people from enrolling as well. The complexity of the forms and translation may make it difficult for inner city individuals to participate in the study.

1. c) A Phase 3 study of a drug to treat renal cell carcinoma in patients who have failed to respond to chemotherapy and radiation therapy. Adult females and males, 18 years and older, are eligible. They must have the disease indication and close to normal range blood cell counts. Patients with compromised kidney functions are not eligible.

This study might have difficulty with enrollment since it is a cancer clinical trial. In some cases, doctors may not tell their patients that a clinical trial is an option for care treatment. Also, it has been suggested that some doctors avoid suggesting a clinical trial to other races or ethnic minorities out of concern that the patients may take offense. In addition, enrollment issues may come from the elderly population being underrepresented. For instance, a physician may be less likely to refer the patient to a clinical trial than a younger patient due to prior cancer history, transportation issues, and a lower level of scientific understanding. The elderly patients may comprise the larger percentage of individuals with the cancer as well, therefore, this present an enrollment issue.

1. d) A Phase 3 trial of a novel pediatric cough/cold preparation. Children of both sexes between the ages of four and twelve are eligible. They must have a cold or cough, and they must have written parental consent to participate. Any children with known sensitivities to the class of drugs to which the investigational compound belongs are excluded.

Clinical trials with pediatric trials are harder to obtain enrollment because the parents are in charge of the consent and may be fearful of the outcome. On the other hand, if it is a last resort, parents may be more willing to try anything and enroll their child in the study. In this case, however, the trial is for a cough/cold and since it may not warrant as a last resort, the enrollment may be lower.

1. e) A Phase 2 cardiac study of an antiarrhythmic drug. Adults of both sexes, 18 years and older, with the disease condition, are eligible. All patients must initially undergo a baseline electrophysiology study (EPS) to determine the nature and severity of the arrhythmia, and a second EPS to evaluate the effect (if any) of the investigational drug.

This clinical trial might have a better enrollment due to the type of drug and the fact that the study is open to all adults with the disease condition. In addition, cardiac disease affects a large number of individuals and therefore opens up the study to a huge sample size.

Discuss the importance of quality in clinical trials. Include the role and responsibilities of the monitor, sponsor, investigator, IRB, and regulatory authorities.

Quality control is important in clinical trials because it assures that the results obtained in the clinical trials that occur are not by chance alone. Therefore, it is extremely important that the team members in a clinical trial measure the quantities, equipment, and keep track of all variables that go into the study, as well as adverse effects that arise from patients during the study. There are different roles and responsibilities for assigned individuals in a clinical trial. The monitor has roles that oversee the clinical research project. The program official approves the procedures that the monitor follows. The monitor mainly focuses on adverse effects and reasons for any type of loss to follow up. In addition, the monitor voices concerns or issues with the trial and provides modifications for trial.

The study as a whole is monitored by both the Investigator and IRB. The Investigator is involved in reviewing the progress of each participant in the study and alerts the IRB when adverse events occur or other problems that occur that could influence the IRB in the decision of whether or not to continue with the trial. In addition, the Investigator’s job to correspond to the program official as well.

The sponsor role in a clinical trial is the finding a principal investigator to oversee the trial. In addition, it is the sponsors ‘role to keep record of the trial up to two years after the trial has been completed, as well as allow access to the FDA.

The role of the regulatory authorities in a clinical trial is to oversee the functions of the trial and what functions have not yet been established, as well as functions that need to be strengthened. In addition, the regulating authorities are responsible for inspecting the individuals who conduct or oversee the study. Furthermore, the regulating authorities are responsible for reviewing complaints about the study and educating the parties conducting and overseeing the clinical trial.

An inexperienced colleague has recently committed to enroll subjects into an eczema trial. To date, their only activity has been to place the above advertisement in their local newspaper. So far they have only managed to enroll three subjects; their target is ten. Your colleague has come to you for advice. List five strategies that would increase their enrollment rate in this case. For each of the five strategies, indicate how effective the strategy is likely to be, and any limitations or problems with the strategy.

In order to increase enrollment rate for the trial, there are some strategies that could be taken, such as increasing time with prospective patients, offer an incentive for trial participants, focus on hope for positive outcomes, provide a physician’s opinion, and explain the randomization process of clinical trials. Focus should begin on spending time with potential patients and thoroughly discussing the details of the trial, risks and benefits. The patients will have a better understanding of the study and may consider enrolling. Offering an incentive, such as a cash payment for participation may increase the likelihood of people enrolling and participating. In addition, if the focus is geared to a positive outcome for the trial, the participants may be enticed to try the clinical trial as it may help their eczema problems. Furthermore, if a patient is given a physician’s opinion on the outcome and on clinical trials in general, they may be more willing. Also, if the clinical trial process is clearly defined, individuals may gain a better general understanding to the benefits that arise from a clinical trial.

Discuss the relationship between GCP, GMP and GLP.

GCP (Good Clinical Practices), GMP (Good Manufacturing Practices), and GLC (Good Laboratory Practices) are all regulations that are governed through the Food and Drug Administration (FDA). The regulations have been implemented in order to ensure the safety of all drugs that are marketed to the public. All of the regulations are similar in that they ensure the quality and safety of the product. In addition, within the regulations, the GCP, GMP and GLP have regulations that must follow the organization and personnel, facilities, equipment, protocols for testing, records, reports and results from non-compliances within these areas.